A Phase 2 Study of ONO-2808 in Patients With Multiple System Atrophy

A Phase 2, Double-blind, Placebo-controlled, Parallel-group Study Followed by an Open-label, Parallel Group Extension Part to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Potential Efficacy of Multiple Doses of ONO-2808 in Patients With Multiple System Atrophy

This is a Phase 2, double-blind, parallel-group, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of multiple doses of ONO-2808 in patients with MSA. This is the first study of ONO-2808 in patients with MSA.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple System Atrophy (MSA)
• Intervention / Treatment: Drug: ONO-2808; Drug: Placebo

Detailed Description

This study will consist of a core part and an extension part. The purpose of the core part is to evaluate 3 doses of ONO-2808 compared to placebo in MSA patients, including: 1) safety and tolerability, 2) pharmacokinetics, and 3) changes in clinical outcome assessments (COA) and biomarkers considered to be related to the pharmacodynamics and potential efficacy of ONO-2808. The purpose of the extension part is to evaluate 3 doses of ONO-2808 in MSA patients, including: 1) safety and tolerability and 2) changes in COAs and biomarkers considered to be related to the pharmacodynamics and potential efficacy of ONO-2808.

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aichi-ken
    • Toyoake, Aichi-ken, Japan
      • Fujita Health University Hospital
  • Kyoto
    • Kyoto, Kyoto, Japan
      • National Hospital Organization Utano National Hospital
  • Miyagi
    • Sendai, Miyagi, Japan
      • National Hospital Organization Sendai Nishitaga Hospital
  • Osaka
    • Toyonaka, Osaka, Japan
      • National Hospital Organization Osaka Toneyama Medical Center
  • Tokyo
    • Fuchū, Tokyo, Japan
      • Tokyo Metropolitan Neurological Hospital
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • The Parkinson's Movement and Disorder Institute
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine at UCLA
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine
  • Colorado
    • Englewood, Colorado, United States, 80113
      • CenExel Rocky Mountain Clinical Research
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine - Yale Church Street Research Unit (CRSU)
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Parkinson's Disease and Movement Disorders Center of Boca Raton
    • Gainesville, Florida, United States, 32608
      • Norman Fixel Institute for Neurological Diseases - University of Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic in Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Emory University School of Medicine
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center Research Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan School of Medicine
    • Farmington Hills, Michigan, United States, 48334
      • QUEST Research Institute
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University
    • New York, New York, United States, 10019
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10016
      • NYU Langone Health - NYU Dysautonomia Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati College of Medicine
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43201
      • Ohio State University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State University - Milton S. Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19107
      • The University of Pennsylvania - Pennsylvania Hospital
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University Medical Center
  • Washington
    • Kirkland, Washington, United States, 98034
      • Evergreen Health
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Institute, Movement Disorders Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female or male patients with a diagnosis of clinically-established or clinically-probable MSA according to the novel Movement Disorder Society (MDS) criteria for MSA diagnosis (2022), including patients with MSA of either subtype (MSA-P or MSA-C).

2. Patients at the early stages of the disease, defined as a maximum of 5 years since the onset of one of the following symptoms associated with MSA:

   • Parkinsonism
   • Ataxia
   • Orthostatic hypotension and/or urinary dysfunction
3. Patients with an anticipated survival of at least 3 years in the opinion of the Investigator.
4. Patients who are able to ambulate without the assistance of another person, defined as the ability to take at least 10 steps and then to turn around and walk at least another 10 steps. Use of assistive devices (e.g., walker or cane) is allowed.
5. Ability to swallow oral medication and be willing to adhere to the study intervention regimen.

Exclusion Criteria:

1. Pregnant or lactating females.
2. Patients with a clinically-significant or unstable medical or surgical condition other than MSA that, in the opinion of the Investigator, might preclude safe completion of the study or might affect the results of the study (e.g., pulmonary, cardiovascular [including bradyarrhythmia], macular edema, and significant renal or hepatic dysfunction).
3. Neurological diseases/disorders other than MSA, such as Parkinson's disease, dementia with Lewy bodies, essential tremor, progressive supranuclear palsy, spinocerebellar ataxia, spastic paraparesis, corticobasal degeneration, or vascular, normal pressure hydrocephalus, pharmacological, or post-encephalitic parkinsonism.
4. Patients with documented liver diseases or cirrhosis.
5. Positive results at Screening for active viral infections that include positive human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, and hepatitis C virus (HCV).
6. Patients with suicide ideation according to the Investigator's clinical judgment per the Columbia Suicide Severity Rating Scale (C-SSRS) at Screening or who have made a suicide attempt in the 6 months before Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo Arm	Drug: Placebo; Oral administration of placebo once a daily for 24 weeks in the core part and 32 weeks total including the extension part; Transition to low-dose of ONO-2808 for remainder of the extension part until week 80
Experimental: ONO-2808 Arm	Drug: ONO-2808; Oral administration of ONO-2808 at low, middle or high doses once a daily for 24 weeks in the core part and 80 weeks total including the extension part

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)	Incidence of TEAEs, drug-related TEAEs, TEAEs resulting in study treatment discontinuation, TESAEs, and drug-related TESAEs will be tabulated by system organ class (SOC), preferred term (PT), and severity.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
Vital signs (blood pressure)	Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
Vital signs (pulse rate)	Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
Vital signs (temperature)	Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
Vital signs (respiratory rate)	Summaries of clinically significant and non-clinically significant abnormalities will be provided by each time point.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
12-lead electrocardiograms (ECGs); parameters such as, but not limited to, heart rate, RR, PR, QRS, QT, and corrected QT intervals (QTcF)	The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of ECG results will be tabulated at each time point.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
Clinically-significant abnormal physical examination findings	The number of patients with normal, abnormal not clinically significant and abnormal clinically significant of physical examination results will be tabulated at each time point.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
Clinical laboratory abnormalities (hematology, clinical chemistry, and urinalysis)	The number of patients with abnormal laboratory results at any time during the study will be tabulated.	From screening up to follow-up for the core part and for the extension part (up to Week 92)
Clinically-abnormal findings in the Columbia Suicide Severity Rating Scale (C-SSRS)	Responses to the suicidality assessment scale (C-SSRS) will be listed.	From screening up to follow-up for the core part and for the extension part (up to Week 92)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of ONO-2808	Descriptive summary statistics will be calculated for ONO-2808 plasma concentrations, by dose level and time point.	Week 2, Week 8, Week 12, and Week 24
ONO-2808 concentration in cerebrospinal fluid (CSF)	Descriptive summary statistics will be calculated for ONO-2808 CSF concentrations, by dose level and time point.	Week 24

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co. Ltd
• Investigators: Study Director: Project Leader, Ono Pharmaceutical Co. Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2023
• Primary Completion (Actual): September 15, 2025
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: June 7, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Basal Ganglia Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Multiple System Atrophy
• Other Study ID Numbers: ONO-2808-03; jRCT2041230153 (Registry Identifier: Japan Registry of Clinical Trials)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No